Testis-specific Arf promoter expression in a transposase-aided BAC transgenic mouse model
| Autor: | Yen Ting Liu, Stephen X. Skapek, Caitlin C. Devitt, Caroline Y. Sung, Lynda Bennett |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Chromosomes Artificial Bacterial Transgene Transposases Mice Transgenic Biology Article Cell Line 03 medical and health sciences Exon Mice 0302 clinical medicine Testis Genetics Animals Humans Kinase activity Promoter Regions Genetic Molecular Biology Gene Transposase Cyclin-Dependent Kinase Inhibitor p16 ADP-Ribosylation Factors General Medicine Cell biology Transgenesis genomic DNA Disease Models Animal 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis Genetically Engineered Mouse |
| Zdroj: | Mol Biol Rep |
| Popis: | CDKN2A is an evolutionarily conserved gene encoding proteins implicated in tumor suppression, ocular development, aging, and metabolic diseases. Like the human form, mouse Cdkn2a encodes two distinct proteins – p16(lnk4a), which blocks cyclin-dependent kinase activity, and p19(Arf), which is best known as a positive regulator of the p53 tumor suppressor – and their functions have been well-studied in genetically engineered mouse models. Relatively little is known about how expression of the two transcripts is controlled in normal development and in certain disease states. To better understand their coordinate and transcript-specific expression in situ, we used a transposase-aided approach to generate a new BAC transgenic mouse model in which the first exons encoding Arf and Ink4a are replaced by fluorescent reporters. We show that mouse embryo fibroblasts (MEFs) generated from the transgenic lines faithfully display induction of each transgenic reporter in cell culture models, and we demonstrate the expected expression of the Arf reporter in the normal testis, one of the few places where that promoter is normally expressed. Interestingly, the TGFβ-2-dependent induction of the Arf reporter in the eye - a process essential for normal eye development - does not occur. Our findings illustrate the value of BAC transgenesis in mapping key regulatory elements in the mouse by revealing the genomic DNA required for Cdkn2a induction in cultured cells and the developing testis, and the apparent lack of elements driving expression in the developing eye. |
| Databáze: | OpenAIRE |
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